Modeling the ligand specific mu- and delta-opioid receptor conformations
Modelovanje konformacija µ- i δ-opioidnih receptora specifičnih za pojedine ligande
Apstrakt
An automated docking procedure was applied to study the binding of a series of mu- and delta-selective ligands to ligand-specific mu- and delta-opioid receptor models. Short-time molecular dynamic simulations were used to obtain ligand-specific mu- and delta-opioid receptors from arbitrarily chosen models of the active form of these receptors. The quality of receptor model depended on the molecular volume of the ligand in the receptor-ligand complex used in the molecular dynamic simulations. Within a series of ligands of similar size (volume), the results of ligand docking to the obtained ligand-specific receptor conformation were in agreement with point mutation studies. The correlation of the calculated and the experimentally determined binding energies was improved in relation to the initial receptor conformation.
Računska metoda automatizovanog dokiranja primenjena je na vezivanje serije liganada, specifičnih za µ- i δ-receptore, za modele ovih receptora. Kratkotrajna molekulsko dinamička simulacija je korišćena za dobijanje konformacija ovih receptora koje su specifične za pojedine ligande, polazeći od slučajno izabranog modela aktiviranog receptora. Kvalitet ovako dobijenog modela receptora zavisi od molekulske zapremine liganda u ligand-receptor kompleksu korišćenog u molekulsko-dinamičkoj simulaciji. Za seriju liganda slične zapremine rezultati dokiranja su u skladu sa eksperimentalnim rezltatima mutacija aminokiselina u receptoru. Korelacija izračunatih i merenih energija vezivanja je poboljšana u odnosu na rezultate dobijene sa polaznom konformacijom receptora.
Ključne reči:
molecular modeling / opioid receptor / opioid receptor / ligand-receptor interactions / ligand-receptor interactions / docking simulation / docking simulationIzvor:
Journal of the Serbian Chemical Society, 2011, 76, 9, 1247-1262Izdavač:
- Serbian Chemical Soc, Belgrade
Finansiranje / projekti:
- Ministry of Education and Science of the Republic of Serbia
DOI: 10.2298/JSC110120110S
ISSN: 0352-5139
WoS: 000295659800007
Scopus: 2-s2.0-80053127358
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Senćanski, Milan AU - Ivanović, Milovan AU - Vuckovic, Sonja AU - Došen-Mićović, Ljiljana PY - 2011 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1207 AB - An automated docking procedure was applied to study the binding of a series of mu- and delta-selective ligands to ligand-specific mu- and delta-opioid receptor models. Short-time molecular dynamic simulations were used to obtain ligand-specific mu- and delta-opioid receptors from arbitrarily chosen models of the active form of these receptors. The quality of receptor model depended on the molecular volume of the ligand in the receptor-ligand complex used in the molecular dynamic simulations. Within a series of ligands of similar size (volume), the results of ligand docking to the obtained ligand-specific receptor conformation were in agreement with point mutation studies. The correlation of the calculated and the experimentally determined binding energies was improved in relation to the initial receptor conformation. AB - Računska metoda automatizovanog dokiranja primenjena je na vezivanje serije liganada, specifičnih za µ- i δ-receptore, za modele ovih receptora. Kratkotrajna molekulsko dinamička simulacija je korišćena za dobijanje konformacija ovih receptora koje su specifične za pojedine ligande, polazeći od slučajno izabranog modela aktiviranog receptora. Kvalitet ovako dobijenog modela receptora zavisi od molekulske zapremine liganda u ligand-receptor kompleksu korišćenog u molekulsko-dinamičkoj simulaciji. Za seriju liganda slične zapremine rezultati dokiranja su u skladu sa eksperimentalnim rezltatima mutacija aminokiselina u receptoru. Korelacija izračunatih i merenih energija vezivanja je poboljšana u odnosu na rezultate dobijene sa polaznom konformacijom receptora. PB - Serbian Chemical Soc, Belgrade T2 - Journal of the Serbian Chemical Society T1 - Modeling the ligand specific mu- and delta-opioid receptor conformations T1 - Modelovanje konformacija µ- i δ-opioidnih receptora specifičnih za pojedine ligande VL - 76 IS - 9 SP - 1247 EP - 1262 DO - 10.2298/JSC110120110S ER -
@article{ author = "Senćanski, Milan and Ivanović, Milovan and Vuckovic, Sonja and Došen-Mićović, Ljiljana", year = "2011", abstract = "An automated docking procedure was applied to study the binding of a series of mu- and delta-selective ligands to ligand-specific mu- and delta-opioid receptor models. Short-time molecular dynamic simulations were used to obtain ligand-specific mu- and delta-opioid receptors from arbitrarily chosen models of the active form of these receptors. The quality of receptor model depended on the molecular volume of the ligand in the receptor-ligand complex used in the molecular dynamic simulations. Within a series of ligands of similar size (volume), the results of ligand docking to the obtained ligand-specific receptor conformation were in agreement with point mutation studies. The correlation of the calculated and the experimentally determined binding energies was improved in relation to the initial receptor conformation., Računska metoda automatizovanog dokiranja primenjena je na vezivanje serije liganada, specifičnih za µ- i δ-receptore, za modele ovih receptora. Kratkotrajna molekulsko dinamička simulacija je korišćena za dobijanje konformacija ovih receptora koje su specifične za pojedine ligande, polazeći od slučajno izabranog modela aktiviranog receptora. Kvalitet ovako dobijenog modela receptora zavisi od molekulske zapremine liganda u ligand-receptor kompleksu korišćenog u molekulsko-dinamičkoj simulaciji. Za seriju liganda slične zapremine rezultati dokiranja su u skladu sa eksperimentalnim rezltatima mutacija aminokiselina u receptoru. Korelacija izračunatih i merenih energija vezivanja je poboljšana u odnosu na rezultate dobijene sa polaznom konformacijom receptora.", publisher = "Serbian Chemical Soc, Belgrade", journal = "Journal of the Serbian Chemical Society", title = "Modeling the ligand specific mu- and delta-opioid receptor conformations, Modelovanje konformacija µ- i δ-opioidnih receptora specifičnih za pojedine ligande", volume = "76", number = "9", pages = "1247-1262", doi = "10.2298/JSC110120110S" }
Senćanski, M., Ivanović, M., Vuckovic, S.,& Došen-Mićović, L.. (2011). Modeling the ligand specific mu- and delta-opioid receptor conformations. in Journal of the Serbian Chemical Society Serbian Chemical Soc, Belgrade., 76(9), 1247-1262. https://doi.org/10.2298/JSC110120110S
Senćanski M, Ivanović M, Vuckovic S, Došen-Mićović L. Modeling the ligand specific mu- and delta-opioid receptor conformations. in Journal of the Serbian Chemical Society. 2011;76(9):1247-1262. doi:10.2298/JSC110120110S .
Senćanski, Milan, Ivanović, Milovan, Vuckovic, Sonja, Došen-Mićović, Ljiljana, "Modeling the ligand specific mu- and delta-opioid receptor conformations" in Journal of the Serbian Chemical Society, 76, no. 9 (2011):1247-1262, https://doi.org/10.2298/JSC110120110S . .
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